Because of an increasing awareness that the frequency of inborn errors of the five enzymes of the urea cycle may be greater than previously supposed, methods will be developed for prenatal diagnosis and for screening newborn infants and mentally retarded children. Metabolic studies will be done in animal models of these diseases and in patients so as to permit optimum therapy designed to reduce the requirement for urea production to minimal levels. This therapy will consist of protein restriction plus various mixtures of essential amino acids and their nitrogen free analogues.